Salivary Gland Secretion Mechanisms During Normal and Altered Functional States

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The health of the oral cavity is maintained by salivary secretions. Our past studies have focused on understanding mechanisms of saliva formation and their alteration during pathologic processes, and developing novel methods to treat salivary dysfunction. During this reporting period we have continued our efforts to utilize gene transfer technology to alter the phenotypic behavior of salivary epithelial cells. Specifically, we have continued efforts to correct the salivary damage suffered by patients whose salivary glands are exposed to radiation during treatment for head and neck cancer. We have extended past findings using the recombinant adenovirus AdhAQP1 which leads to increased fluid secretion in irradiated rats. These new efforts have concentrated on the mechanism by which hAQP1 enhances fluid secretion and on its application to primate glands. Additionally, we have made progress in the application of recombinant adeno-associated virus constructs for salivary gland gene transfer. We have also extended studies on the systemic secretion of transgene products from transduced salivary epithelial cells. Using a dwarf mouse model, we showed that glands infected with a recombinant adenovirus encoding mouse growth hormone secrete therapeutic levels of the hormone. Additionally, this virus, AdmGH, can lead to a doubling of dwarf mouse size in 30 days after a single intramuscular injection.